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Sp5 transcription factor

Mark W Kennedy, Ravindra B Chalamalasetty, Sara Thomas, Robert J Garriock, Parthav Jailwala, Terry P Yamaguchi
The ancient, highly conserved, Wnt signaling pathway regulates cell fate in all metazoans. We have previously shown that combined null mutations of the specificity protein (Sp) 1/Klf-like zinc-finger transcription factors Sp5 and Sp8 (i.e., Sp5/8) result in an embryonic phenotype identical to that observed when core components of the Wnt/β-catenin pathway are mutated; however, their role in Wnt signal transduction is unknown. Here, we show in mouse embryos and differentiating embryonic stem cells that Sp5/8 are gene-specific transcriptional coactivators in the Wnt/β-catenin pathway...
March 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
Jimin Pei, Nick V Grishin
Specificity proteins (SPs) and Krüppel-Like Factors (KLFs) are C2H2-type zinc finger transcription factors that play essential roles in differentiation, development, proliferation and cell death. SP/KLF proteins, similarly to Wilms tumor protein 1 (WT1), Early Growth Response (EGR), Huckebein, and Klumpfuss, prefer to bind GC-rich sequences such as GC-box and CACCC-box (GT-box). We searched various genomes and transcriptomes of metazoans and single-cell holozoans for members of these families. Seven groups of KLFs (KLFA-G) and three groups of SPs (SPA-C) were identified in the three lineages of Bilateria (Deuterostomia, Ecdysozoa, and Lophotrochozoa)...
November 15, 2015: Gene
Stephanie M Perez, David D Aguilar, Jennifer L Neary, Melanie A Carless, Andrea Giuffrida, Daniel J Lodge
Both environmental and genetic factors contribute to schizophrenia; however, the exact etiology of this disorder is not known. Animal models are utilized to better understand the mechanisms associated with neuropsychiatric diseases, including schizophrenia. One of these involves gestational administration of methylazoxymethanol acetate (MAM) to induce a developmental disruption, which in turn produces a schizophrenia-like phenotype in post-pubertal rats. The mechanisms by which MAM produces this phenotype are not clear; however, we now demonstrate that MAM induces differential DNA methylation, which may be heritable...
January 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
S H Lee, R Luong, D T Johnson, G R Cunha, L Rivina, M L Gonzalgo, Z Sun
Emerging evidence has demonstrated the critical roles for both androgen and Wnt pathways in prostate tumorigenesis. A recent integrative genomic analysis of human prostate cancers (PCas) has revealed a unique enrichment of androgen and Wnt signaling in early-onset PCas, implying their clinical significance in the disease. Additionally, interaction between the androgen receptor (AR) and β-catenin has long been detected in PCa cells. However, the consequence of this interaction in prostate tumorigenesis is still unknown...
February 11, 2016: Oncogene
William C Dunty, Mark W L Kennedy, Ravindra B Chalamalasetty, Kenneth Campbell, Terry P Yamaguchi
Neuromesodermal (NM) stem cells reside in the primitive streak (PS) of gastrulating vertebrate embryos and generate precursors of the spinal cord and musculoskeletal system. Although Wnt3a/β-catenin signaling is crucial for NM stem cell maintenance and differentiation, few key transcriptional effectors have been identified. Through a concerted transcriptional profiling and genetic approach we have determined that two Zn(2+)-finger transcription factors, Sp5 and Sp8, are regulated by Wnt3a in the PS, and are essential for neural and musculoskeletal patterning...
2014: PloS One
Dong-Seok Park, Jeong-Han Seo, Mina Hong, Wonseon Bang, Jin-Kwan Han, Sun-Cheol Choi
BACKGROUND: The neural crest (NC) is a multipotent embryonic cell population, which is induced by an integration of secreted signals including BMP, Wnt, and FGF and, subsequently, NC cell fates are specified by a regulatory network of specific transcription factors. This study was undertaken to identify a role of Sp5 transcription factor in vertebrates. RESULTS: Xenopus Sp5 is expressed in the prospective neural crest regions from gastrulation through the tadpole stages in early development...
December 2013: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Nate P Hoverter, Ju-Hui Ting, Suman Sundaresh, Pierre Baldi, Marian L Waterman
The lymphoid enhancer factor 1/T cell factor (LEF/TCF) family of transcription factors are downstream effectors of the WNT signaling pathway, which drives colon tumorigenesis. LEF/TCFs have a DNA sequence-specific high-mobility group (HMG) box that binds Wnt response elements (WREs). The "E tail" isoforms of TCFs are alternatively spliced to include a second DNA binding domain called the C-clamp. We show that induction of a dominant negative C-clamp version of TCF1 (dnTCF1E) induces p21 expression and a stall in the growth of DLD1 colon cancer cells...
September 2012: Molecular and Cellular Biology
M Felcht, M Heck, C Weiss, J C Becker, E Dippel, C S L Müller, D Nashan, M M Sachse, J P Nicolay, N Booken, S Goerdt, C-D Klemke
BACKGROUND: Primary cutaneous B-cell lymphomas (PCBCL) are subdivided into the aggressive form, primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL, LT) and two subtypes of indolent behaviour (primary cutaneous follicle centre lymphoma and primary cutaneous marginal zone B-cell lymphoma). The difference in clinical behaviour can be explained by the tumour cell itself, or the lymphoma microenvironment including the antitumour immune response. OBJECTIVES: To investigate the presence of regulatory T cells (Treg), CD4+CD25+FOXP3+, in the microenvironment of PCBCL in correlation with clinical outcome...
August 2012: British Journal of Dermatology
Martin E Fernandez-Zapico, Gwen A Lomberk, Shoichiro Tsuji, Cathrine J DeMars, Michael R Bardsley, Yi-Hui Lin, Luciana L Almada, Jing-Jing Han, Debabrata Mukhopadhyay, Tamas Ordog, Navtej S Buttar, Raul Urrutia
SP/KLF (Specificity protein/Krüppel-like factor) transcription factors comprise an emerging group of proteins that may behave as tumour suppressors. Incidentally, many cancers that display alterations in certain KLF proteins are also associated with a high incidence of KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue) mutations. Therefore in the present paper we investigate whether SP/KLF proteins suppress KRAS-mediated cell growth, and more importantly, the potential mechanisms underlying these effects...
April 15, 2011: Biochemical Journal
Yusuke Marikawa, Dana Ann A Tamashiro, Toko C Fujita, Vernadeth B Alarcon
Transcription factor Oct4 is expressed in pluripotent cell lineages during mouse development, namely, in inner cell mass (ICM), primitive ectoderm, and primordial germ cells. Functional studies have revealed that Oct4 is essential for the maintenance of pluripotency in inner cell mass and for the survival of primordial germ cells. However, the function of Oct4 in the primitive ectoderm has not been fully explored. In this study, we investigated the role of Oct4 in mouse P19 embryonal carcinoma (EC) cells, which exhibit molecular and developmental properties similar to the primitive ectoderm, as an in vitro model...
April 2011: Stem Cells and Development
Nina D Schaeper, Nikola-Michael Prpic, Ernst A Wimmer
BACKGROUND: The Sp-family of transcription factors are evolutionarily conserved zinc finger proteins present in many animal species. The orthology of the Sp genes in different animals is unclear and their evolutionary history is therefore controversially discussed. This is especially the case for the Sp gene buttonhead (btd) which plays a key role in head development in Drosophila melanogaster, and has been proposed to have originated by a recent gene duplication. The purpose of the presented study was to trace orthologs of btd in other insects and reconstruct the evolutionary history of the Sp genes within the metazoa...
2010: BMC Evolutionary Biology
Setsuko Sahara, Yasuhiko Kawakami, Juan Carlos Izpisua Belmonte, Dennis D M O'Leary
Telencephalic patterning centers, defined by the discrete expression domains of distinct morphogens, Fgfs in the commissural plate (CoP), Wnts and Bmps in the cortical hem, and a ventral domain of Sonic hedgehog (Shh), are postulated to establish during development the initial patterning of the telencepahlon, including the neocortex. We show that the expression patterns of Sp5, Sp8, and Sp9, members of the Sp8-like family that are homologues of Drosophila buttonhead, correlate during early embryonic development with these three telencephalic patterning centers...
2007: Neural Development
Naoko Fujimura, Tomas Vacik, Ondrej Machon, Cestmir Vlcek, Simone Scalabrin, Martin Speth, Dzung Diep, Stefan Krauss, Zbynek Kozmik
Wnt/beta-catenin signaling regulates many processes during vertebrate development. To study transcriptional targets of canonical Wnt signaling, we used the conditional Cre/loxP system in mouse to ectopically activate beta-catenin during central nervous system development. We show that the activation of Wnt/beta-catenin signaling in the embryonic mouse telencephalon results in the up-regulation of Sp5 gene, which encodes a member of the Sp1 transcription factor family. A proximal promoter of Sp5 gene is highly evolutionarily conserved and contains five TCF/LEF binding sites that mediate direct regulation of Sp5 expression by canonical Wnt signaling...
January 12, 2007: Journal of Biological Chemistry
Yongxin Chen, Yingqiu Guo, Xijin Ge, Hirotaka Itoh, Akira Watanabe, Takeshi Fujiwara, Tatsuhiko Kodama, Hiroyuki Aburatani
In this report, we describe the expression and function of human Sp5, a member of the Sp family of zinc finger transcription factors. Like other family members, the Sp5 protein contains a Cys2His2 zinc finger DNA binding domain at the C-terminus. Our experiments employing Gal4-Sp5 fusion proteins reveal multiple transcriptional domains, including a N-terminal activity domain, an intrinsic repressive element, and a C-terminal synergistic domain. Elevated expression of Sp5 was noted in several human tumors including hepatocellular carcinoma, gastric cancer, and colon cancer...
February 17, 2006: Biochemical and Biophysical Research Communications
Meiko Takahashi, Yusuke Nakamura, Kazutaka Obama, Yoichi Furukawa
Mutations in APC, CTNNB1, AXIN1 or AXIN2 cause impairment in the beta-catenin degradation pathway and result in accumulation of beta-catenin in a wide range of human cancers. Accumulated beta-catenin then associates with Tcf/LEF transcription factors and transactivates their target genes. To uncover in detail the role of accumulated beta-catenin in colorectal carcinogenesis, we searched for genes involved in the beta-catenin/Tcf signaling pathway by cDNA microarray. We identified and characterized a human gene, SP5, that was down-regulated after depletion of beta-catenin by transduction of wild-type APC into SW480 cells...
December 2005: International Journal of Oncology
Gilbert Weidinger, Chris J Thorpe, Katrin Wuennenberg-Stapleton, John Ngai, Randall T Moon
BACKGROUND: Wnt/beta-catenin signaling regulates many processes during vertebrate development, including patterning of the mesoderm along the dorso-ventral axis and patterning of the neuroectoderm along the anterior-posterior axis during gastrulation. However, relatively little is known about Wnt target genes mediating these effects. RESULTS: Using zebrafish DNA microarrays, we have identified several new targets of Wnt/beta-catenin signaling, including sp5-like (sp5l, previously called spr2), a zinc-finger transcription factor of the Sp1 family...
March 29, 2005: Current Biology: CB
Shigehiro Kuraku, Ryo Usuda, Shigeru Kuratani
The turtle shell is an evolutionary novelty in which the developmental pattern of the ribs is radically modified. In contrast to those of other amniotes, turtle ribs grow laterally into the dorsal dermis to form a carapace. The lateral margin of carapacial primordium is called the carapacial ridge (CR), and is thought to play an essential role in carapace patterning. To reveal the developmental mechanisms underlying this structure, we systematically screened for genes expressed specifically in the CR of the Chinese soft-shelled turtle, Pelodiscus sinensis, using microbead-based differential cDNA analysis and real-time reverse transcription-polymerase chain reaction...
January 2005: Evolution & Development
O Keith Okamoto, J Woodland Hastings
In this study, the effects of 1 mM sodium nitrite, a reactive nitrogen species (RNS) generator, and 0.5 mM paraquat, which produces reactive oxygen species (ROS), on gene expression in the marine dinoflagellate species Pyrocystis lunula were investigated using microarrays containing 3500 complementary DNAs (cDNAs). A total of 246 differentially expressed genes were identified under these treatments: 204 genes were specifically regulated in response to nitrite and 37 genes specifically to paraquat. Only six genes showed a dependence on both nitrite and paraquat, indicating that the two agents act predominantly via distinct pathways...
December 4, 2003: Gene
Olga Ossipova, Reimer Stick, Tomas Pieler
Proteins related to the human transcription factor Sp1 are characterized by the presence of a highly conserved zinc finger domain consisting of three C2H2 type zinc fingers. Here we describe two Xenopus laevis cDNAs, which encode novel Sp1-related C2H2 type zinc finger transcription factors named XSPR-1 and XSPR-2. Structurally, XSPR-1 and XSPR-2 are closely related to the murine Sp5, which interacts genetically with Brachyury (Dev. Biol. 227 (2000) 358). XSPR-1 and XSPR-2 are expressed in broad and dynamic patterns during early development...
July 2002: Mechanisms of Development
D Treichel, M B Becker, P Gruss
We describe the sequence and expression pattern of Sp5, a novel member of the vertebrate Sp1 transcription factor gene family which consists of at least five members. This gene family is characterized by a highly conserved domain which is formed by three Zn fingers, which bind to the GC box or the GT/CACC box in the promoter of many genes. These boxes are important cis-acting elements required for the expression of the respective genes. In vitro experiments indicate that the Sp1 transcription factors act by influencing the methylation state of the DNA, or by direct interactions with other promoter specific transcription factors...
March 2001: Mechanisms of Development
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